{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T12:55:36Z","timestamp":1793105736091,"version":"4.5.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:00:00Z","timestamp":1688601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Currently the responses of peripheral cytokine-secreting cells in the natural course of human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection haven\u2019t been fully elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The function of peripheral proinflammatory, regulatory and cytotoxic cytokine-secreting cells were investigated by direct intracellular cytokine staining (ICS) and flow cytometry, additionally, the absolute numbers of different cytokine-secreting cells were measured among patients with HIV\/TB co-infection (HT group), and compared them with the healthy controls (HC group), patients with TB (TB group) and patients with HIV infection (HIV group). After one week\u2019s anti-TB treatment, the changes of the percentages of cytokine-secreting cells were further evaluated in TB and HT groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Totally 26 individuals in the HC group, 51 in the TB group, 26 in the HIV group and 29 in the HT group were enrolled. The HT. HT group exhibited significantly lower absolute numbers of IFN-\u03b3<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup>, IFN-\u03b3<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup>, TNF-\u03b1<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup>, IL17A<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> T cells and TNF-\u03b1<jats:sup>+<\/jats:sup>CD14<jats:sup>+<\/jats:sup> monocytes than the TB and HIV groups. Compared with the TB group, the percentages of CD8<jats:sup>+<\/jats:sup> T cells secreting IFN-\u03b3 and perforin (p=0.010; p=0.043) were significantly lower among the HT group. Compared with the HIV group, the percentages of CD4<jats:sup>+<\/jats:sup>, CD8<jats:sup>+<\/jats:sup> T cells and CD14<jats:sup>+<\/jats:sup> monocytes secreting TNF-\u03b1 (p=0.013; p=0.001; p&amp;lt;0.001) were significantly decreased, and the percentage of CD8<jats:sup>+<\/jats:sup> T cells secreting IL-17A (p=0.015) was significantly increased among the HT group. Both the percentages of CD4<jats:sup>+<\/jats:sup> T cells secreting TGF-\u03b2 (p&amp;lt;0.001; p=0.001), and CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells secreting granzyme A (all p&amp;lt;0.001), were significantly higher among the HT group than among the TB group and HIV group. After one week\u2019s anti-TB treatment, an increased percentage of CD4<jats:sup>+<\/jats:sup> T cells secreting TNF-\u03b1 (p=0.003) was found in the TB group, and an increased percentage of CD8<jats:sup>+<\/jats:sup> T cells secreting TNF-\u03b1 (p=0.029) was found in the HT group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Significantly different functional profiles of peripheral proinflammatory, regulatory, and cytotoxic cytokine-secreting cells were observed in the natural course of HIV\/TB co-infection compared to TB and HIV infection alone, even though the absolute numbers of those cells were significantly lower in HIV\/TB co-infection. TNF-\u03b1-secreting CD8<jats:sup>+<\/jats:sup> T cells may be a more sensitive marker for early evaluation of anti-TB treatment efficacy in patients with HIV\/TB co-infection.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2023.1162420","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T19:15:52Z","timestamp":1688670952000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Characterization of peripheral cytokine-secreting cells responses in HIV\/TB co-infection"],"prefix":"10.3389","volume":"13","author":[{"given":"Yuting","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihui","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanni","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songjie","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajun","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqi","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2454","DOI":"10.1128\/jvi.78.5.2454-2459.2004","article-title":"Human CD4+ CD25+ regulatory T cells control T-cell responses to human immunodeficiency virus and cytomegalovirus antigens","volume":"78","author":"Aandahl","year":"2004","journal-title":"J. Virol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1111\/j.1365-2249.2005.02976.x","article-title":"Cytokine profile during latent and slowly progressive primary tuberculosis: a possible role for interleukin-15 in mediating clinical disease","volume":"143","author":"Abebe","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1086\/517479","article-title":"Selective increase in plasma tumor necrosis factor-alpha and concomitant clinical deterioration after initiating therapy in patients with severe tuberculosis","volume":"178","author":"Bekker","year":"1998","journal-title":"J. Infect. Dis."},{"key":"B4","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1038\/nrmicro.2017.128","article-title":"Pathogenesis of HIV-1 and mycobacterium tuberculosis co-infection","volume":"16","author":"Bell","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"10.1111\/joim.12778","DOI":"10.1111\/joim.12778","article-title":"Friends and foes of tuberculosis: modulation of protective immunity","volume":"27","author":"Brighenti","year":"2018","journal-title":"J. Internal Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1016\/j.smim.2014.09.008","article-title":"Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-gamma immunity","volume":"26","author":"Bustamante","year":"2014","journal-title":"Semin. Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1007\/s12013-014-0125-z","article-title":"Expression of TNF-alpha, IFN-gamma, TGF-beta, and IL-4 in the spinal tuberculous focus and its impact on the disease","volume":"70","author":"Chen","year":"2014","journal-title":"Cell Biochem. Biophys."},{"key":"B8","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1007\/s15010-022-01789-9","article-title":"Diagnostic accuracy of the interferon-gamma release assay in acquired immunodeficiency syndrome patients with suspected tuberculosis infection: a meta-analysis","volume":"50","author":"Chen","year":"2022","journal-title":"Infection"},{"key":"B9","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.jinf.2014.06.009","article-title":"Polyfunctional T-cells and effector memory phenotype are associated with active TB in HIV-infected patients","volume":"69","author":"Chiacchio","year":"2014","journal-title":"J. Infect."},{"key":"B10","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.tube.2015.07.002","article-title":"Interferon gamma release assays for monitoring the response to treatment for tuberculosis: a systematic review","volume":"95","author":"Clifford","year":"2015","journal-title":"Tuberculosis (Edinb)"},{"key":"B11","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.tube.2015.01.003","article-title":"Cytokines for monitoring anti-tuberculous therapy: a systematic review","volume":"95","author":"Clifford","year":"2015","journal-title":"Tuberculosis (Edinb)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1089\/jir.2018.0164","article-title":"Transforming growth factor-\u03b2 suppresses interleukin (IL)-2 and IL-1\u03b2 production in HIV-tuberculosis Co-infection","volume":"39","author":"Devalraju","year":"2019","journal-title":"J. Interferon Cytokine Res."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2022.2045852","article-title":"Granzyme b(+) CD4 T cells accumulate in the colon during chronic HIV-1 infection","volume":"14","author":"Dillon","year":"2022","journal-title":"Gut Microbes"},{"key":"B14","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.coi.2019.04.013","article-title":"Granulysin: killer lymphocyte safeguard against microbes","volume":"60","author":"Dotiwala","year":"2019","journal-title":"Curr. Opin. Immunol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1159\/000283687","article-title":"Association of antigen-stimulated release of tumor necrosis factor-alpha in whole blood with response to chemotherapy in patients with pulmonary multidrug-resistant tuberculosis","volume":"80","author":"Eum","year":"2010","journal-title":"Respiration"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.745592","article-title":"Differential diagnosis of latent tuberculosis infection and active tuberculosis: a key to a successful tuberculosis control strategy","volume":"12","author":"Gong","year":"2021","journal-title":"Front. Microbiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1164\/rccm.200508-1294OC","article-title":"Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis","volume":"173","author":"Guyot-Revol","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1097\/00002030-199905280-00009","article-title":"Dynamics of plasma cytokine levels in patients with advanced HIV infection and active tuberculosis: implications for early recognition of patients with poor response to anti-tuberculosis treatment","volume":"13","author":"Hsieh","year":"1999","journal-title":"AIDS"},{"key":"B19","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1084\/jem.20032069","article-title":"CD25(+)CD4(+) regulatory T cells from the peripheral blood of asymptomatic HIV-infected individuals regulate CD4(+) and CD8(+) HIV-specific T cell immune responses in vitro and are associated with favorable clinical markers of disease status","volume":"200","author":"Kinter","year":"2004","journal-title":"J. Exp. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1016\/j.tube.2014.06.007","article-title":"Altered CD8(+) T cell frequency and function in tuberculous lymphadenitis","volume":"94","author":"Kumar","year":"2014","journal-title":"Tuberculosis (Edinb)"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/6587296","article-title":"The immunoregulation of Th17 in host against intracellular bacterial infection","volume":"2018","author":"Li","year":"2018","journal-title":"Mediators Inflamm."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/217287","article-title":"Multifunctional analysis of CD4+ T-cell response as immune-based model for tuberculosis detection","volume":"2015","author":"Lichtner","year":"2015","journal-title":"J. Immunol. Res."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035290","article-title":"Peripheral T cell cytokine responses for diagnosis of active tuberculosis","volume":"7","author":"Nemeth","year":"2012","journal-title":"PloS One"},{"key":"B24","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/nrmicro3230","article-title":"In search of a new paradigm for protective immunity to TB","volume":"12","author":"Nunes-Alves","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02502","article-title":"A low frequency of IL-17-Producing CD8(+) T-cells is associated with persistent immune activation in people living with HIV despite HAART-induced viral suppression","volume":"9","author":"Perdomo-Celis","year":"2018","journal-title":"Front. Immunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1002\/eji.201243262","article-title":"Mycobacterium tuberculosis-specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease","volume":"43","author":"Rozot","year":"2013","journal-title":"Eur. J. Immunol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3564","DOI":"10.1016\/j.celrep.2019.11.034","article-title":"Compromised metabolic reprogramming is an early indicator of CD8(+) T cell dysfunction during chronic mycobacterium tuberculosis infection","volume":"29","author":"Russell","year":"2019","journal-title":"Cell Rep."},{"key":"B28","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.cellimm.2015.10.009","article-title":"Regulation of CD8+ T-cell cytotoxicity in HIV-1 infection","volume":"298","author":"Saeidi","year":"2015","journal-title":"Cell Immunol."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0158262","article-title":"Tuberculosis therapy modifies the cytokine profile, maturation state, and expression of inhibitory molecules on mycobacterium tuberculosis-specific CD4+ T-cells","volume":"11","author":"Saharia","year":"2016","journal-title":"PloS One"},{"key":"B30","doi-asserted-by":"publisher","first-page":"377","DOI":"10.2147\/JIR.S172878","article-title":"Regulatory T cells antagonize proinflammatory response of IL-17 during cutaneous tuberculosis","volume":"11","author":"Saini","year":"2018","journal-title":"J. Inflammation Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.diagmicrobio.2016.01.006","article-title":"Granzyme b as a diagnostic marker of tuberculosis in patients with and without HIV coinfection","volume":"85","author":"Sarkar","year":"2016","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"B32","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1086\/513769","article-title":"Clinical correlates of interferon gamma production in patients with tuberculosis","volume":"25","author":"Sodhi","year":"1997","journal-title":"Clin. Infect. Dis."},{"key":"B33","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1186\/s12879-022-07807-3","article-title":"Frequency and functional profile of circulating TCR\u03b1\u03b2(+) double negative T cells in HIV\/TB co-infection","volume":"22","author":"Tan","year":"2022","journal-title":"BMC Infect. Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1097\/INF.0000000000000109","article-title":"Intracellular cytokine and cathelicidin secretion from monocytes and neutrophils in childhood tuberculosis","volume":"33","author":"Torun","year":"2014","journal-title":"Pediatr. Infect. Dis. J."},{"key":"B35","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1038\/nri3839","article-title":"Perforin and granzymes: function, dysfunction and human pathology","volume":"15","author":"Voskoboinik","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079431","article-title":"Mycobacterium tuberculosis-specific TNF-\u03b1 is a potential biomarker for the rapid diagnosis of active tuberculosis disease in Chinese population","volume":"8","author":"Wang","year":"2013","journal-title":"PloS One"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.840610","article-title":"T Cell metabolism in infection","volume":"13","author":"Wik","year":"2022","journal-title":"Front. Immunol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e00426","DOI":"10.1128\/IAI.00426-18","article-title":"Low levels of T cell exhaustion in tuberculous lung granulomas","volume":"86","author":"Wong","year":"2018","journal-title":"Infect Immun."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2022.895179","article-title":"The role of CD4(+)CD8(+) T cells in HIV infection with tuberculosis","volume":"10","author":"Zou","year":"2022","journal-title":"Front. Public Health"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.1071880","article-title":"Phenotype and function of peripheral blood \u03b3\u03b4 T cells in HIV infection with tuberculosis","volume":"12","author":"Zou","year":"2022","journal-title":"Front. Cell Infect. Microbiol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1162420\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T19:15:54Z","timestamp":1688670954000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1162420\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,6]]},"references-count":40,"alternative-id":["10.3389\/fcimb.2023.1162420"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2023.1162420","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,6]]},"article-number":"1162420"}}